The six investigators working together on this Program Project are studying various cardiovascular and respiratory adaptations to hypoxia. The phenomenon of hypoxic pulmonary hypertension is being investigated as to physiological mechanisms, chemical mediators, cellular mediators, and basis for individual variability, and the site of vasoconstriction in the pulmonary microcirculation. Additional studies of the pulmonary circulation relate to pressor substances in amniotic fluid which may be the chemical mediators of pulmonary vasoconstriction in the fetus. Oxygen transport in the face of chronic hypoxia is being investigated in both man and animal. The mechanisms responsible for the increase in cardiac output during acute hypoxia are poorly understood, and these are being explored systematically in the dog. Further studies include the potential advantages and disadvantages of secondary polycythemia. A basis for the reduction in cardiac output following adaptation to high altitude is being sought through studies of myocardial contractility in the goat. Since this affect of hypobaric hypoxia cannot be duplicated by comparable degrees of hypoxemia induced by carbon monoxide, we are examining the potential importance of hypocapnia and alkalosis which are associated aspects of exposure to high altitude. When hypocapnia is prevented, hypobaric hypoxia does not decrease cardiac output. Since hypoxia causes an increase in pulmonary ventilation through stimulation of the carotid body, factors which modify carotid body function are being explored. Some of these investigations include human subjects with marked variations in hypoxic ventilatory drive. The influence of altering oxygen uptake and/or body temperature is being explored. In many of these areas of investigation, a variety of forms of hypoxia are being compared, including airway hypoxia, anemia, carbon monoxide, and alterations in blood flow. Results of these investigations have obvious application in a wide variety of human states including normal man at high altitude.